DESCRIPTION: Discovery of structurally novel and potentially very important anticancer drugs from animal, plant and microorganism sources followed by their synthesis and/or structural modification will form the sharply focused objective of this research for the U.S. National Cancer Institute (NCI) . Special emphasis will be placed on new antineoplastic substances either isolated based on molecular target bioassays or subsequently displaying such potent antiangiogenesis, tubulin and/or various cancer-implicated kinase (cyclin-dependent, protein kinase C, tyrosine kinase and telomerase) properties as well as exceptionally strong antineoplastic activity. Additional emphasis will be placed on further research necessary to advancing the expanding clinical trials of bryostatin 1, the dolastatins, and others we discovered such as the powerful cancer antiangiogenesis drug combretastatin A-4 phosphate. vigorous parallel research will be strongly focused on the isolation, characterization, and structural determination of new and potentially useful anticancer drugs from confirmed active extracts of marine invertebrates (and vertebrates) , marine and terrestrial plants, and marine as well as terrestrial microorganisms. Only those species that give maximum promise of yielding new drugs with potential clinical activity will be pursued. The proposed research will provide great assistance to the DCTD/NCI in selecting new anticancer drug candidates and speeding their development toward clinical trial. In summary, the proposed research will be sharply aimed at the discovery and very rapid development of new anticancer drugs for the NCI programs directed at improving human cancer treatments.